Specific areas of research in this program project include: adaptive response of cells to the carcinogen/mutagen MNNG; role of MNNG-adaptation to DNA repair processes and protection against carcinogens/mutagens; the role of post-replication methylation in fixing alkylation induced mutations; repair of O-alkylated pyrimidines; molecular aspects of gene regulation by the cyclic AMP-dependent protein kinase system of lymphoma cells; cAMP-mediated alteration of cellular proteins; metabolism and structural studies of kinase regulatory subunits; translation discrimination by cytoplasmic regulatory proteins; the relationship of stored mRNP to polysomal mRNA; characterization and function of translational control (tc) RNA; assembly mechanism for membrane-viruses; alterations in cellular gene expression by abnormal proteins; non-glycosylated membrane-associated viral protein; transcriptional and translational mapping of viral genomes; the role of phosphorylated proteins of viruses; phosphorylation of ribosome-associated components in virus-infected cells; mechanism of inhibition of cellular macromolecular synthesis by viruses; phosphorylation of protein synthesis initiation factor; host factors in viral interference; the interferon system, mechanism of action and induction; dsRNA as the interferon inducer moiety of viruses; the mechanism(s) of cell killing by viruses; cell persistence in persistent infection; homotypic defective-particle interference; genetic cloning of defective-interfering particles; cell sparing by interferon action; intrinsic interference. Viruses and virus mutants used include: vesicular stomatitis, Sindbis, reovirus, mengo, herpes, pseudorabies, rabies defective particles, rubella, Newcastle disease, and vaccinia. Cell lines used include: mouse S49 lymphoma, mouse C3H/10T1/2, GMK-Vero and BSC, BHK, human trisomic 21, HeLa, HEp2 and mouse L (Y).